1. Field of the Invention
This invention relates broadly to medical articles and devices. More particularly, this invention relates to methods of treating the surface of the medical article or devices to affect the surface structure thereof, and medical articles and devices having such modified surface structure.
2. State of the Art
Metals and metal alloys, and particularly titanium and titanium alloys, are used for a great variety of implantable articles for medical applications. Among these applications are: structural articles which are used to repair or replace or reinforce bones or to reconstruct joints; structural articles to expand and reinforce arterial, vascular, and other body structures with lumens; wire embolization coils for occluding arteries; enclosures for pacemakers, defibrillators, and implantable infusion pumps; pacing leads; wire sutures and ligatures; staples; filters to catch thrombi and emboli; and, so forth. All implantable articles suffer from some degree of bio-incompatibility, which may be manifested as tissue inflammation, necrosis, hyperplasia, mutagenicity, toxicity, and other reactions, such as attack by giant cells and leukocytes, and macrophages. While titanium and its alloys are generally considered inert when implanted, some biological and biochemical interactions still may occur, and others have found it desirable to provide various coatings on the surface of titanium and titanium alloy implants for certain purposes. The same holds true for many other metals and metal alloys.
In the area of vascular stents others have coated stents (whether made of titanium or other materials) with biological agents (such as genetic material or cellular material) or chemical agents (such as anti-proliferation reagents or cell-growth factors) to reduce problems associated with hyperplasia or inflammation. In order to attach these biological or chemical agents to the surface of a metallic stent, the agents have been mixed with binders such as elastomers or bio-resorbable polymers. These binders can also create problems in that they can cause inflammation, and they can cause the surface of the stent to have more friction, which reduces the ease of stent delivery.
In the field of dental and orthopedic implants, there are sometimes problems associated with acceptance of the implant by body tissues. These problems may be ameliorated by adding anti-inflammatory agents to the surface of the implant. Also, it has been shown that for some implants, it is advantageous for the surface of the implant to be microporous to allow ingrowth of either soft tissue or hard tissue (bone) to enhance the anchoring of the implant in the body. Such microporous surfaces are generally created by attaching a layer of sintered spherical powders to selected surfaces of the implant in areas where tissue ingrowth is desired.
However, attachment of these sintered-powder layers requires additional processing steps, and there is a practical limit to the size of pores that can be achieved. Also, the temperature at which the powders must be sintered approaches the melting point of the material, and the implant is left in a fully-annealed condition, which may be lower in strength than desired. Also, sintered-powder coatings on titanium articles must be applied in a high-temperature, high-vacuum furnace, which is necessarily an expensive and labor-intensive process.
In the field of implanted electrodes, it has been found that sintered powder coatings enhance the attachment of the electrodes and help them to retain a low-impedance connection to the tissue. Such electrodes are generally manufactured by machining an electrode component, applying a multiple-layer coating of powdered metal in an organic binder, and sintering the coated electrode in a controlled-atmosphere (or high vacuum) furnace.
Other medical implants, such as vena-cava filters, aneurism clips, staples, and sutures, are constructed of wire and thus have a relatively large surface area for their size. Accordingly, methods which allow the addition of biological and biochemical agents to the surface of the implant may be advantageous in minimizing the adverse reactions of body tissues with the implant.
Another type of implant, embolization coils, are intended to cause thrombosis so that arteries may be blocked off to mitigate the danger of an aneurism or to deny the blood supply to a tumor. In such devices it may be advantageous to apply biological or chemical agents to the surface of the coils in order to enhance the formation of thrombus.
In the field of arterial stents, coatings have been applied to stainless steel and titanium alloys (e.g., TiNi alloys) to retard tissue reactions such as thrombosis, inflammation, and hyperplasia. Such coatings have been based upon stable bio-compatible polymers (such as styrene-isobutylene-styrene (SIBS)) and bio-resorbable polymers, such as polyglycolic acid. In the work known to date, the active chemical or biological agent is mixed with the polymeric coating material, and the agent then elutes from the coating once the implant is placed in the body.
U.S. Pat. No. 5,972,027 relates to a stent formed of graded layers of powdered metal, with some of the surface layers formed of powder made of larger particle sizes. Once the stent has been sintered, the major portion of the stent is consolidated to a substantially solid form, but that portion of the surface that was made with larger particle-size powder remains microporous. In this way, a stent is manufactured so that at least some parts of the surface are microporous and can be infiltrated with a biological or chemical agent. Such a process is very difficult, since the stent must be made from a xe2x80x9cgreenxe2x80x9d preform that is very thin. The finished thickness of an arterial stent ranges from approximately 50 to 125 microns (or approximately 0.002 to 0.005 inches), and the microporous surface layer would be only a fraction of that thickness. Such a thin preform would be very fragile and difficult to handle prior to being sintered.
Other techniques have been described for creating a micro-microporous surface on a metallic article, and such processes might be used for creating a microporous coating on a metallic implant. Such processes include ion milling, photo-chemical machining, electro-discharge machining, and micro-machining using conventional cutting tools.
Of these methods, only the first two are suitable for creating a large number of very small pores (micropores), in the range of 1 to 50 microns in size. Such methods are more suitable for application to flat substrates because they rely on optical or quasi-optical processes. It would be difficult and expensive to apply these processes to small non-flat articles, such as stents, bone screws, dental implants, and clips.
The last three methods are suitable for creating larger pores or pockets in the surface of implants, but such larger pores would require the chemical or biological agent to be bound to the article by means of some binding agent, usually a polymer.
Thus, all of the known methods require either very expensive processes to produce a fine microporous structure, or else it is necessary to use a binding material to attach the biological or chemical agent to the implant article.
It is therefore an object of the invention to provide a process for modifying the surface of a metal or metal alloy implant to create a microporous surface layer thereon.
It is another object of the invention to provide a process for particularly modifying the surface of a titanium or titanium alloy implant to create a microporous surface layer thereon.
It is a further object of the invention to provide a process for creating a microporous surface on an implant article that could be preferentially applied to only a desired portion of the surface of the implant.
It is also an object of the invention to provide an efficient process which would create a fine microporous structure on the surface of an implant article that would allow a biological or chemical agent to be infiltrated into the surface of the article without the need for binding agents.
In accord with these objects, which will be discussed in detail below, a process for creating a microporous layer on the surface of a titanium or titanium alloy medical device comprises the following steps. The device is cleaned to ensure that it is free of any surface contaminants that could react with and diffuse into the metal when it is heated. A surface layer of titanium oxide or titanium oxy nitride is then created on the surface of the device. According to a preferred reduction process to produce a porous layer at the location of the oxide layer, the oxidized titanium device is placed into a bath of molten calcium chloride and connected to the negative terminal of an electrical power supply. The positive terminal of the electrical power supply is connected to a suitable anode preferably immersed in or containing the molten calcium chloride. An electrical current is then passed through the electrolytic cell. After a time, the titanium device is removed from the molten salt bath, allowed to cool, and rinsed with purified water to remove any surface salt. If necessary, the resulting titanium device may be etched to remove any thin layer of titanium oxide which may have formed during the cooling process. The above described process is suitable where it is desired to modify substantially the entire surface of a medical device.
According to another embodiment, only a designated portion of the surface of a medical device is made microporous. This is done by one of by several techniques. According to a first technique, an area which is not to be treated is masked. The non-masked surface is then subject to oxidation. The remainder of the process is then as described above. According to a second technique, the entire surface of the device is oxidized. The oxidation layer is then selectively removed by etching. The oxide layer is then reduced as described above. According to a third technique, the device may be oxidized and processed through the process as described above so that the entire surface area is made microporous. Then, selected areas of the microporous surface layer may be removed by any subtractive process, such as etching, machining, grinding, etc. With the above techniques, it is possible to produce a titanium or titanium alloy device which has only selected areas of its surface having a microporous structure, and the remaining areas consisting of its base material.
In addition, the processes described can be used on medical devices made of other metal or metal alloy substrate materials. Examples of alternative substrates include reactive and refractory metals, cobalt alloys, nickel alloys, and stainless steel alloys.
Further, other reduction processes can be used to reduce the oxide layer to a metallic layer, including direct reduction by means of an active metal, electrochemical reduction in mixed molten salts, and electrochemical reduction in non-aqueous solvents.
Additional objects and advantages of the invention will become apparent to those skilled in the art upon reference to the detailed description taken in conjunction with the provided figures.